Balanced pressure process of sterilization

ABSTRACT

THE PROCESS DISCLOSED HEREIN DEALS WITH STERILIZING GOODS PACKAGE OF SEMI-PERMEABLE CONTAINERS IN A PERMEABLE GAS (ETHYLENE OXIDE). AN IMPERMEABLE GAS IS ADDED TO THE ATMOSPHERE OF PERMEABLE GAS AND THIS OVER-PRESSURE OF THE IMPERMEABLE GAS IS USED TO CONFINE THE PACKAGE SO THAT NO SWELLING OF THE PACKAGE CAN OCCUR. AIR MAY BE USED AS THE IMPERMEABLE GAS TO PROVIDE THE CONFINING OVERPRESSUR. THIS CONFINING PRESSURE BALANCES THE EFFECT OF THE PARTIAL PRESSURE OF THE PERMEATED GAS WITHIN THE PACKAGE SO THAT THE PACKAGE CANNOT INFLATES BEYOND IT ORIGINAL SIZE.

June 29, 1911 QAGUNTHER 3,589,861

- BALANCED PRESSURE PROCESS OF STERILIZATION Filed May 20, 1968 4 Sheets-Sheet l 0\ Q '8 N w June 29, 1971 v GUNTHER I 3,589,861

BALANCED PRESSURE PROCESS 0F STERILIZATION Filed May 20. 1968 4 Sheets-Sheet 8 FIG.

INVENTOR. DONALD A. mmm

BY aka/W June 29, 1971 u. A. GUNTHER 3,589,861

BALANCED PRESSURE PROCESS OF STERILIZATION Filed May 20. 1968 4. Sheets-Sheet s DONALD A. Gun 7745K INVENTOR.

June 29, 1971 o. A. GUNTHER BALANCED PRESSURE PROCESS OF STERILIZATION Filed May 20. 1968 4. Sheets-Sheet TIME IN HouRS INVENTOR DONALD A. Gun/THE)? a a FIG;

ATTORNEY United States Patent 3,589,861 BALANCED PRESSURE PROCESS OF STERILIZATION Donald A. Gunther, Erie, Pa., assignor to American Sterilizer Company, Erie, Pa. Filed May 20, 1968, Ser. No. 730,311 Int. Cl. A611 1/00 U.S. Cl. 21-58 25 Claims ABSTRACT OF THE DISCLOSURE The process disclosed herein deals with sterilizing goods packaged in semi-permeable containers in a permeable gas (ethylene oxide). An impermeable gas is added to the atmosphere of permeable gas and this over-pressure of the impermeable gas is used to confine the package so that no swelling of the package can occur. Air may be used as the impermeable gas to provide the confining overpressure. This confining pressure balances the effect of the partial pressure of the permeated gas Within the package so that the package cannot inflate beyond its original s1ze.

THE PROBLEM A semi-permeable membrane is a membrane that is permeable to certain liquids or gases, i.e., certain liquids or gases will pass through the membrane, but others will not.

Polyethylene is an example of a material that is permeable to certain gases, including ethylene oxide, but is essentially impermeable to other gases including air. Other examples of membranes permeable to certain sterilizing gases yet impermeable to other gases, such as air, are nylon and cellophane.

Thus, when a sealed polyethylene package is placed in an environment of a permeable sterilizing gas, such as ethylene oxide, with an arbitrarily chosen pressure of p.s.i., ethylene oxide will flow through the polyethylene until the ethylene oxide reaches an equilibrium whereby the partial pressure of the ethylene oxide on the inside of the package becomes equal to the pressure of the ethylene oxide on the outside of the package, or 15 p.s.i. To this partial pressure of ethylene oxide inside the package would be added the partial pressure of residual air already in the package and hence, the package will contain a greater pressure than the surrounding atmosphere. The package or packages, being flexible, will tend to swell and exert a corresponding pressure.

If the material or the seal of such a package is weak, the package may rupture as swelling occurs; if such a package is relatively strong, compared to a confining package such as a cardboard box, the pressure developed within the swelling packages will rupture the cardboard box. Intermediate effects could also be observed.

The swelling of such a semi-permeable package placed in an atmosphere of a permeable gas is due to Grahams Law regarding the diffusion of gases, described as the tendency for a gas to distribute uniformly throughout the space available to it; and to Daltons Law of partial pressures, wherein each gas in a mixture of non-reacting gases exerts its own partial pressure in a container independent of the other gases and the total pressure of the mixture in the container is equal to the sum of the partial pressures of each independent acting gas. The partial pressure of each gas is that pressure that each gas would exert if it occupied the container alone. Therefore, if a package, such as polyethylene, is permeable to the gas, this gas will permeate the package in an attempt to reach uniform distribution (equilibrium) according to Grahams Law; the sum of the partial pressure of the permeated gas in the package, and the partial pressure of the residual air in ice the package, is greater than the pressure of the sterilizing gas outside the package, and hence, the package tends to swell in response to this pressure differential created by the residual air within the package that cannot escape. Water vapor, commonly used in ethylene oxide sterilization, has its own partial pressure and contributes, along with the partial pressure of ethylene oxide, to the total pressure in the sterilizing atomsphere; since water vapor permeates polyethylene, the partial pressure of the water vapor will contribute, along with ethylene oxide and air, to the total pressure within the polyethylene package. The magnitude of the respective partial pressures is dependent on the concentration of each component gas present.

This invention is a technique that was specifically designed to prevent the swelling of sealed polyethylene packages during the sterilization cycle as a result of the permeating gas. To this end, an external pressure is applied to the package to balance the partial pressure of the permeated sterilizing gas on the inside of the package, thus preventing the package from swelling due to this added internal pressure. Air is used as an impermeable gas to provide a confining over-pressure. This permeable confining pressure balances the pressure of the permeating sterilizing gas (including water vapor and diluent gases) so that the package cannot swell beyond its original size, despite the fact that the permeating gas reaches a concentration (pressure) equilibrium within the package; this equilibrium is manifested by an increase in pressure within the package that is counteracted by the confining im permeable pressure outside the package, and hence, no change in the size of the package will occur. The overpressure of the impermeable gas must, therefore, be equal to or greater than the sum of the partial pressures of all the component gases that have permeated the package at any given time. Assuming sufficient permeating time to reach equilibrium within the package, then, the absolute partial pressure of the impermeable gas in the sterilizing chamber atmosphere must be equal to or greater than the sum of the absolute partial pressures of the permeable sterillizing gases in the chamber atmosphere.

PRIOR METHODS Techniques such as the common air displacement-atmospheric pressure cycle are incapable of preventing the problem of semi-permeable package swelling because such a technique simply avoids the added'problem of swelling due to expansion of residual air when a vacuum is drawn. The permeation of a sterilizing gas will still occur and the degree of swelling and inclination of the package to burst will be dependent upon the concentration of the sterilizing gas in the chamber and the exposure time. By prior techniques, the degree of swelling or tendency to rupture can only be controlled by the strength of the package or by sacrificing sterilizing effect through the use of low gas concentration or short exposure time. Such techniques then cannot more than compromise an otherwise normal cycle.

POST-DIFFUSION With the Balanced Pressure technique disclosed herein, the same concentration of gas must equilibrate within the package as would occur without the balanced over-pressure and will become equal to the permeable gas pressure outside the package. However, this equilibrium will be manifested only 'by an increase in pressure within the package with no attendant swelling of the package. If the cycle were completed at this time and the balanced over-pressure removed, the permeated gas within the package would again manifest itself by swelling the package to some degree due to the pressure differential created. Therefore, it is desirable to incorporate in the cycle a post-diffusion period whereby the permeable gas is flushed from the chamber with the impermeable gas (for example, air), maintaining a balanced over-pressure, and holding this condition for a period of time to allow the permeable gas to diffuse back out of the package. During this flushing and post-diffusion period, the impermeable gas must maintain a gauge pressure equal to or greater than the absolute partial pressure of the permeale gas within the package or the package will inflate.

Since no film is absolutely impermeable to any gas, particularly if there are defects in the film, the post-diffusion period may be programmed to decrease in pressure over the time period so as to minimize the possible entrance of traces of impermeable gas into the package. The programmed pressure decrease has been determined by experiment and coincides with the pressure decrease Within the package as the permeable gas permeates out of the package during the post-diffusion period.

Since the sterilization reaction is occurring during th.: primary exposure period due to permeation into the package, and during the post-diffusion period while permeation out of the package occurs, the total sterilizing reaction is a function of time and gas concentration inside the package during both of these periods.

All phases of the cycle are carried out at greater than atmospheric pressure and no vacuum pumps are required; however, a source of pressurized air is required. The concentration of the sterilizing agent is limited only by the pressure capability of the vessel.

MOISTURIZATION The nature of most industrial packages are such that a timed, in-chamber, moisture pre-conditioning period is valueless and moisture may be added immediately before, during, and/or immediately after introduction of the sterilizing gas. In addition, studies have revealed that a controlled moderate moisture concentration, for example, 50% to 60% relative humidity, is not required and, as a consequence, complicated electronic controls have been eliminated in the cycle disclosed. In fact, these studies also show that a high moisture concentration is most effective. Current sterilizing techniques now exploit this principle and the system disclosed herein senses this condition by a vapor pressure measurement with a simple pressure gauge.

It is, accordingly, an object of the present invention to provide an improved process for sterilizing sealed packages made of semi-permeable membrane material in a permeable gas.

Another object of the invention is to provide a sterilizing process for sterilizing goods in semi-permeable packages with a permeable microbicidal gas wherein a nonpermeable gas in the chamber around the package is used to balance the partial pressure of the permeable gas that permeates into the package, adding its partial pressure to residual air already in the package.

Still another object of the invention is to provide an improved sterilizing cycle.

With the above and other objects in view, the invention comprises the processes set forth in the specification and drawings and recited in the appended claims. It is understood that minor details may be changed without departing from the invention. The invention will be better understood from a reference to the drawings and detailed specification wherein:

FIG. 1 is a front isometric view of a sterilizer suitable for carrying out the process according to the invention;

FIGS. 2 and 3 are side isometric views of the sterilizer shown in FIG. 1;

FIG. 4 is a graph of typical cycles according to the invention; and

FIG. 5 is a schematic view of a chamber that could be used in the process disclosed herein.

An apparatus in which the balanced pressure process according to the invention can be carried out is shown in FIG. 5. Any suitable chamber can be used that is equipped with gas supply for sterilization, air or other nonpermeable gas for over-pressure and, if desired, steam for moisturization. There is shown in FIG. 5 diagrammatically a sterilizing chamber of double walled cylindrical type with its axis arranged horizontally. The wall is shown at 201, and the space within the wall constitutes a sterilizing chamber 8. One end of the sterilizing chamber is provided with a door 207 which can be locked in an airtight manner by manipulating a handle 209, so as to seal the sterilizing chamber 8 to enable any desired pressure, within the sterilizing range, to be built up therein.

The construction of the sterilizing chamber, jacket, and door may allbe conventional.

Within the chamber may be any suitable support for the articles to be sterilized; for example, a shelf 211 on which packages of goods 213 may be placed.

A steam supply conduit 221 is connected to any suitable source of supply of steam at any pressure convenient to the establishment where the sterilizing apparatus is located, so long as the temperature and pressure of the steam are at least as high as the highest temperature and pressure that will be wanted in the sterilizer for moisturization of the goods, or for heating. Conveniently, the steam may be at a gage pressure of about 27 p.s.i., corresponding to a temperature of about 270 degrees F.

The steam for use in the sterilizer for moisturization or heating passes from the supply line or conduit 221 through a manual shut-off valve 7 controlled by a handle 223 accessible near the front of the sterilizer.

Gas may be admitted, FIG. 2, from conventional bottles through lines 271. The gas in the bottle may be at a pressure of approximately 800 p.s.i.g. and may be reduced in pressure by a suitable regulator to approximately 15 pounds per square inch, or the desired pressure.

The compressed air supply conduit is indicated at 251 in FIG. 5 and is connected to any suitable source of compressed air having a pressure at least as high as the highest pressure that will be wanted within the sterilizing chamber under normal operating conditions to provide the desired over-pressure. The supply conduit leads to an adjustable pressure reducing valve.

A drainage conduit 261 leads downwardly from the bottom and regulators are provided for programming postdiffusion. I

Mounted at a conveniently visible and accessible position near the front of the sterilizer are the controls and timers for primary exposure and post-diffusion of any Zuigable conventional construction, indicated generally at As shown in FIGS. 2 and 3, electricity for operating the various solenoid valves and other equipment is supplied from a bus bar 300 which has the branch lines 301, 302, 303, 304, 305, 306, 307, 308, and 309 supplying the various valves, motors, and other control equipment with electricity. The motor 253 drives the pump 265. Safety valves 266 are provided to protect the inside of the chamber from excessively high pressures. Gas from lines 271 is connected to the inside of the sterilizer through line 275, FIG. 2, by way of the several regulator valve and gauge assemblies indicated at 276 supported on a stand 277. Air for overpressure and post-diffusion is controlled by valve 252 and filter element 253. The air may be supplied from a compressed air source from line 254 or introduced into line 255 by pump 265 which is connected to line 255. The various portions of the cycle may be manually controlled from the control panel 256 which has (FIG. 3) control buttons 257 of the type familiar to those skilled in the art.

The sterilizer chamber and controls shown in FIG. 1 are of the conventional type and are shown by way of example only.

The drawing, FIG. 4, shows a typical cycle showing an abscissa 11 and representing time in hours and an ordinate 10 representing pressure.

In FIG. 4, the portion of the graph indicated at 21 indicates the time at which water vapor is admitted to approximately .025 p.s.i.g. to the point 12. The conditioned gas for sterilizing can then be admitted to bring the pressure up to say lbs. indicated at B, portion 22 of the curve, or it can be admitted to say lbs. in another example indicated at B of the curve. The gas pressure will then be held at a relatively constant value, for example, 10 p.s.i.g. indicated at C or 15 p.s.i.g. indicated at C. The pressure will then be reduced in the chamber from 15 p.s.i.g. over the solid line portion of the curve indicated at D to the portion E Where it will be held for a period say of 15 minutes at, for example, 8 /2 p.s.i.g. The pressure will then be reduced to, for example, approximately 4 p.s.i.g. at F and held for a period of, for example, one hour and then reduced to atmospheric at the point 20.

The dotted line indicated at D", E", and F and the curves indicated at D, E and F indicate how the pressures in the chamber can be reduced in stages and held at some intermediate pressure for some periods of time to allow the pressure inside the package to normalize itself.

In the process from which the graph, FIG. 4, was taken, a polyethylene bag, indicated at 213, for example, containing air at zero gage and containing goods to be sterilized, is inserted in a sealed chamber 8, as shown in FIG. 5.

In a typical cycle, after loading the package in the chamber and closing the door and all valves except the gas admission valve 270, the valve 270 is opened and the conditioned microbicidal gas mixture is admitted directly to the chamber to a pressure of 15 p.s.i.g. gage. The temperature in the chamber is to be approximately 55 degrees centigrade or 130 degrees Fahrenheit, the relative humidity 60100%. It will be noted that the atmosphere of air originally within the chamber is trapped and retained rather than removed. This air serves as the confining impermeable gas.

After a suitable exposure time, the sterilizing gas is flushed from the sterilizer by the addition of impermeable gas (air) from line 251 while maintaining a pressure within the sterilizer of approximately 15 pounds per square inch gage. A rapid flushing of the sterilizing gas followed by a constant bleed of air to exhaust vent 291 at a chamber pressure of 15 pounds per square inch throughout the post-diffusion period will provide the necessary ambient condition. The pressure outside exhaust vent 291 is atmospheric. A programmed decreasing pressure in which the pressure in the chamber is decreased at a predetermined rate is sometimes desirable and preferred over the constant pressure conditions.

Actual exposure and post-diifusion time will depend upon the wall thickness, durometer of polyethylene, and other properties of the polyethylene from which the pack age is made and must be determined for the individual case.

In the system disclosed, the atmospheric air within the chamber may be removed by the displacement or flushing with the sterilizing gas and the chamber subsequently charged to the desired pressure (concentration) with this sterilizing gas or gas mixture. Common sterilizing gases that may be used are:

(1) Ethylene oxide. (2) Propylene oxide. (3) Methyl bromide. (4) Betapropiolactone.

Common sterilizing gas mixtures are:

(5) 10% ethylene oxide, 90% carbon dioxide, sometimes referred to as Carboxide.

(6) ethylene oxide, 80% carbon dioxide, known in the trade as Oxfume 20.

(7) 12% ethylene oxide, 88% dichlorodifluoromethane,

known as Pennoxide.

(8) 11% ethylene oxide, 79% trichlorofluoromethane, and 10% dichlorodifluoromethane, known as Cryoxcide.

(9) 11% ethylene oxide, 54% trichlorofluoromethane, dichlorodifluoromethane, known as Benvicide.

The above gases and gas mixtures will permeate sealed packages made of semi-permeable material and cause inflation of these ackages. Instead of using air as the nonpermeble gas, an over-pressure of an impermeable gas such as nitrogen or argon may be introduced around the package at a pressure as to confine the package and prevent inflation of the package. At the end of a primary exposure period, the sterilizing gas or gas mixture is flushed out of the chamber with the impermeable gas. This confining pressure with the impermeable gas may be maintained until the permeable sterilizing gas or gas mixture has diffused back out of the package, thus preventing inflation of the package during and after the sterilizing cycle.

In an optimum practical cycle, air, being nearly impermeable, is used as the confining gas. Furthermore, since air is used as the impermeable gas, it is expedient to leave the atmospheric air Within the chamber and add the sterilizing gas or gas mixture to the desired pressure without flushing. If the sterilizing gas or gas mixture is added to a pressure of greater than one atmospere (14.7 p.s.i.a.), that pressure in excess of one atmosphere must be balanced by an additional equivalent amount of air pressure.

The primary exposure period will obviously vary for the different type of loads; wrappers of different thicknesses and other properties.

At the beginning of the post-diffusion period, air or other impermeable gas is admitted to the chamber at a pressure equivalent to the sterilizing pressure, for example, 15 p.s.i.g., and flows through the chamber at a rate sufficient to remove all gas within one hour. Experiments indicate that a minimum flow of air of one chamber volume per thirty minutes is required; the flow should be adjusted at the initial pressure and allowed to drift as the pressure is programmed down.

The cycle using 15 p.s.i.g. chamber pressure is the preferred cycle and will satisfactorily process most packages. An alternate cycle of 10 p.s.i.g. chamber pressure may be used for those packages that cannot be satisfactorily processed at the higher pressure.

In a typical cycle, the chamber temperature was 115 degrees Fahrenheit, the chamber humidity 75%, and the center of load degrees Fahrenheit.

The normal sterilizing cycle will utilize a concentration of 450 ml. of ethylene oxide per liter. This will require 15 to 17 p.s.i.g. chamber pressure. Special cycles may utilize lower or higher pressures. Sterilizing temperature will be between and degrees Fahrenheit; higher and lower temperatures may be used in special applications.

A package of catheters sealed in a polyethylene bag and a package of pipettes sealed in semi-permeable membrane containing six (6) Spordex sterility indicators was enclosed in each load.

Example I (1) Water vapor (steam) was admitted to obtain a relative humidity as close to 100% as possible.

(2) Ethylene oxide gas was admitted to bring chamber pressure to 15 p.s.i.g. and at a concentration of 450 ml. per liter.

(3) The chamber and contents were heated to 130 Fahrenheit.

(4) The pressure in chamber was held at 15 p.s.i.g. and temperature of gas at 130 Fahrenheit for 3 /2 hours.

(5 Air was admitted to chamber while allowing gas to bleed out, maintaining chamber pressure at 15 p.s.i.g. for sixty (60) minutes.

(6) Pressure in chamber was reduced to 8 p.s.i.g. and held for one (1) hour, continuing to bleed air out.

(7) Pressure in chamber was reduced to 4 p.s.i.g. and held for one 1) hour, continuing to bleed air out.

(8) Pressure in chamber was reduced to atmospheric and goods removed.

All the sterility indicators were negative.

7 Examples II through XI (1) Remove atmospheric air from chamber by displacement or flushing with sterilizing gas.

(2) Charge chamber to a pressure of 15 p.s.i.g. with a gas taken from the group of one of the following:

(3) Introduce one of the following impermeable gases at an additional pressure of approximately 2 p.s.1.g.:

(a) Air. (b) Nitrogen.

(4) Heat to 130 Fahrenheit. (5) Hold sterilizer chamber at said pressure for 1% hours.

(6) Plush out permeable gas from chamber with nonpermeable gas.

Example XII Load charged as in Example I.

(1) Admit water vapor (steam) to the chamber at 1 p.s.i.g. to obtain a relative humidity of 75%.

(2) Admit ethylene oxide gas to bring chamber pressure to p.s.i.g. and at a concentration of 450 milligrams per liter.

(3) Heat to 130 degrees Fahrenheit.

(4) Hold pressure in chamber at 15 p.s.i.g. and temperature of gas at 130 degrees Fahrenheit for 3.5 hours.

(5) Admit air to chamber while allowing gas to bleed out, maintaining chamber pressure at 15 p.s.i.g. for 70 minutes.

(6) Reduce pressure in chamber to 8 p.s.i.g. and hold for 70 minutes continuing to bleed air out.

(7) Reduce pressure in chamber to 4 p.s.i.g. and hold for 70 minutes continuing to bleed air out.

(8) Reduce pressure in chamber toatmospheric and remove goods.

Example XIII Load chamber as in Example I, with chamber containing an impermeable gas.

(1) Admit water vapor (steam) over a period of 15 minutes to obtain a vapor pressure of 1.5 p.s.i.g. to obtain maximum absorption of the load without soaking.

(2) Admit ethylene oxide gas to bring chamber pressure to 10 p.s.i.g. and at a concentration of 300 milligrams per liter.

( 3) Heat to 130 degrees Fahrenheit.

(4) Hold pressure in chamber at 10 p.s.i.g. and temperature of gas at 130 degrees Fahrenheit for 3.5 hours.

(5) Admit air to chamber while allowing gas to bleed out, maintaining chamber pressure at 10 p.s.i.g. -for 70 minutes.

(6) Reduce pressure in chamber to 5 p.s.i.g. and hold rfor 70 minutes continuing to bleed air out.

(7) Reduce pressure in chamber to 2.5 p.s.i.g. and hold :for 70 minutes, continuing to bleed air out.

(8) Reduce pressure in chamber to atmospheric and remove goods.

Example XIV Load chamber as in Example I. (1) Admit water vapor (steam) to the chamber to obtain a relative humidity of 75 (2) Admit ethylene oxide gas to bring chamber pressure to 15 p.s.i.g. and at a concentration of 450 milligrams per liter.

( 3) Heat to 130 degrees Fahrenheit.

(4) Hold pressure in chamber at 15 p.s.i.g. and temperature of gas at 130 degrees Fahrenheit for 5 hours.

(5) Admit air to chamber while allowing gas to bleed out, maintaining chamber pressure at 15 p.s.i.g. for minutes.

(6) Reduce pressure in chamber to 8 p.s.i.g. and hold for 100 minutes continuing to bleed air out.

(7 Reduce pressure in chamber to 4 p.s.i.g. and hold for 100 minutes continuing to bleed air out.

(8) Reduce pressure in chamber to atmospheric and remove goods.

Example XV Load chamber as in Example I.

(1) Admit water vapor (steam) to the chamber to obtain a relative humidity of 90% (2) Admit ethylene oxide gas to bring chamber pressure to 15 p.s.i.g. and at a concentration of 450 milligrams per liter.

(3) Heat to degrees Fahrenheit.

(4) Hold pressure in chamber at 15 p.s.i.g. and temperature of gas at 120 degrees Fahrenheit for 2.5 hours.

(5) Admit air to chamber while allowing gas to bleed out, maintaining chamber pressure at 15 p.s.i.g. for 70 minutes.

(6) Reduce pressure in chamber to 8 p.s.i.g. and hold for 70 minutes continuing to bleed air out.

(7) Reduce pressure in chamber to 4 p.s.i.g. and hold for 70 minutes continuing to bleed air out.

(8) Reduce pressure in chamber to atmospheric and 5 remove goods.

0 humidity up to approximately 70 degrees Fahrenheit and 60% relative humidity.

Ethylene oxide was then admitted over the part B of the curve to bring the chamber pressure to approximately 15 p.s.i.g. in the B curve and approximately 10 p.s.i.g. in the B curve. The pressure in the chamber was then retained at this pressure for approximately 3 /2 hours as indicated in the curve at C and C. The chamber temperature was approximately 115 degrees Fahrenheit during the part C and C of the curve. The center of the load rose to between 80 and Fahrenheit. The pressure in the chamber was then reduced, as indicated at D, D and D", and held for a time E, E and E" respectively in the three cycles, as shown. The pressure in the chamber was then reduced as indicated and held for a time F, F and F"; respectively in the three cycles as shown. The pressure in the chamber was then reduced to atmospheric.

In the test indicated by the solid line curve, ethylene oxide at a concentration of approximately 300 milligrams per liter was used and the center of the load rose to between 80 and 103 degrees F. The center of the load had a humidity of 72%, the chamber temperature was F. throughout the test. A Spordex test indicated 6 negative on an equilibrium and a dry test on a desiccated test, which indicated 6 positive. When a tile, placed at the center of the load, having spores thereon, and catheters packaged in polyethylene bags, the test indicated 6 negative on an equilibrium basis and 6 positive on a desiccated basis. In this test, a total exposure of 3 /2 hours was used and a post-diffusion period of 3 /2 hours was likewise used.

In a similar test, the sterilizer chamber was preheated to 130 Fahrenheit. Water vapor was admitted as in the first test described next above and a conventional 8/ 12 Cryoxide mixture was introduced at a concentration of approximately 300 mg./1iter and a 3 /2 hour sterilizing cycle was used and a 3 /2 hour post-diffusion cycle was used. The results were as indicated above with no appreciable swelling of the polyethylene bags.

The tests indicated by the broken line curve indicate a moisturization during the period A, a holding period of approximately 4 hours with a 60100% relative humidity in unconfined polyethylene bags and a 4 hour post-diffusion period. The bags were confined in cardboard boxes. The cardboard boxes were intact at the end of the test and the bags were of the approximate original size.

In all comparative tests using cycles used in the trade where air was first removed from the chamber before introducing ethylene oxide when goods were packaged in polyethylene bags and sterilized in ethylene oxide gas or other permeable gas, the bags burst during the sterilizing cycle.

The foregoing specification sets forth the invention in its preferred practical forms but the structure shown is capable of modification within a range of equivalents without departing from the invention which is to be understood is broadly novel as is commensurate with the appended claims.

The embodiments of hte invention in which an exclusive property or privilege is claimed are defined as follows:

1. A process of sterilizing comprising the steps of placing the goods in a sealed package made of semipermeable material and containing a residual impermeable gas,

introducing a permeable microbicidal sterilizing gas into a chamber at a temperature of approximately 130 degrees Fahrenheit to bring the pressure in said chamber to a predetermined pressure,

providing an impermeable gas in said chamber at a pressure which when added to the absolute pressure of said permeable gas will be substantially equal to the sum of the absolute partial pressure of said residual impermeable gas in said package and the absolute partial pressure of said permeable gas in said package,

holding said permeable gas in said chamber at said predetermined pressure for a sterilizing cycle time sufficient for said permeable gas to permeate into said package and effect sterilization,

and reducing the partial pressure of said permeable gas in said chamber to zero pounds per square inch gauge.

2. The process recited in claim 1 wherein the air is removed from said chamber before said impermeable gas is introduced into said chamber.

3. The process recited in claim 1 wherein said permeable sterilizing gas is taken from the group consisting of ethylene oxide, propylene oxide, methyl bromid, and betapropiolactone.

4. The process recited in claim 1 wherein said impermeable gas is taken from the group consisting of nitrogen and air.

5. The process recited in claim 1 wherein said impermeable gas comprises residual air in said chamber around said package.

6. The process recited in claim 1 wherein water vapor is placed in said chamber prior to said sterilizing cycle.

7. The process recited in claim 1 wherein the relative humidity of said gas in said chamber is increased to between 60% and 100% prior to said sterilizing cycle.

8. The process recited in claim 1 wherein said package is made of a material taken from the group of polyolefin polymers.

9. The process recited in claim 1 wherein after said permeable gas has premeated said package,

the permeable gas is flushed from said chamber by an impermeable gas which is the same impermeable gas as said just mentioned impermeable gas.

10. The process recited in claim 1 wherein said permeable gas is ethylene oxide and said impermeable gas is air.

10 11. The process recited in claim 1 wherein said permeable gas is introduced to said chamber,

raising said predetermined pressure to approximately 15 pounds per square inch gauge.

12. The process recited in claim 11 wherein said permeable gas is held at said predetermined pressure for approximately two to four hours.

13. The process recited in claim 1 wherein said permeable gas is heated to a temperature of approximately 104 degrees Fahrenheit to 130* degrees Fahrenheit and held at approximately said temperature during said sterilizing cycle.

14. The process recited in claim 13 wherein the relative humidity of said gas in said chamber is increased to between 60% and prior to said sterilizing cycle.

15. The process recited in claim 14 wherein said permeable gas is held at said predetermined pressure for approximately two to four hours.

16. The process recited in claim 14 wherein said impermeable gas is placed in said chamber to bring the total chamber pressure to a value at least as great as the total pressure in said package when said permeable gas has premeated into said package to an equilibrium condition with the permeable gas in said chamber.

17. The process of sterilizing comprising providing a sealed chamber,

placing goods in a sealed package made of semi-permeable membrane and containing a residual impermeable admitting an impermeable gas in said chamber,

admitting a permeable microbicidal sterilizing gas to said chamber at a temperature of approximately degrees Fahrenheit to bring the pressure in said chamber to approximately 15 pounds per square inch gage;

exposing said goods to said permeable gas for a suitable exposure time,

and flushing said permeable gas from said chamber with an impermeable gas.

18. The process recited in claim 17 wherein the temperature in said chamber is approximately 55 degrees centigrade during said exposure part of said cycle,

and the relative humidity in said chamber is between 60 and 100 percent.

19. The process recited in claim 17 wherein steam is admitted to said chamber to increase the relative humidity in said chamber prior to admission of said permeable gas.

20. The process recited in claim 17 wherein the pressure of said impermeable gas is reduced to atmospheric at a predetermined rate over a predetermined time.

21. The process recited in claim 20 wherein said predetermined time is approximately two hours,

and said impermeable gas is first reduced to approximately 8 p.s.i.g. then held at approximately 8 p.s.i.g. for approximately /2 hour then reduced to approximately 4 p.s.i.g. and held at this pressure for approximately /2 hour, then reduced to atmospheric pressure.

22. A process of sterilizing comprising providing a sealed chamber containing air at atmospheric pressure,

placing goods to be sterilized in a sealed semi-permeable package in said chamber,

introducing steam into said chamberat a rate to provide maximum absorption by said goods without soaking until said chamber is at approximately 1.5 p.s.i.g.,

admitting a microbicidal sterilizing gas selected from the group consisting of ethylene oxide, propylene oxide, methyl bromid, and betapropiolactone to bring the pressure in said chamber to a predetermined pressure, and a temperature of approximately 130 degrees,

1 1 holding said gas at said predetermined pressure for a References Cited predetermmed tune, UNITED STATES PATENTS flushing permeable gas from said chamber with air, and reducing the pressure in said chamber to substan- 2,398,082 4/1946 cayalhto tially atmospheric pressure in a predetermined time. 5 2,536,115 1/1951 W1,1bur 2156UX 2,3. The process recited in claim 22 wherein 2,868,616 1/1959 Poltras, 21 '2X said steam is introduced to said chamber for approxi- 12/1959 camanus et a1 21*58UX mately 15 minutes- 3,068,064 12/1962 McDonald 21-58 3,093,449 6/1963 Kotarski et al. 21-56X 24. The process recited in claim 23 wherein said microbicidal gas is admitted to said chamber over 10 JOSEPH SCOVRONEK Primary Examiner a period of approximately 45 minutes.

25. The process recited in claim 24 wherein MILLMAN Asslstant Exammer steam is added to maintain vapor pressure in said U S Cl X R chamber at 1.5 p.s.i.g. for a predetermined time prior 21 93 to admitting said microbicidal gas. 15 

